Matritech, Inc. is the manufacturer of a bladder cancer test, NMP22, that is one of only 6 cancer diagnostic tests ever approved by the FDA. A second test, NuMA, for the monitoring of colon cancer, is now in clinical trials. In both tests, the antigen detected is a protein called NuMA. The experiments proposed here are designed to examine high molecular weight NuMA complexes. These complexes will be analyzed by analytical ultracentrifugation. Components of the NuMA complex willbe identified by protein microsequencing, and single chain Fv antibodies willbe made by panning against native NuMA complexes or purified NuMA- associated proteins using naive phage display libraries. Of particular interest is the observed separation of NuMA complexes present in mitotic cells from NuMA complexes observed only in interphase cells. Antibodies to these and other diagnostic markers will be incorporated into improved diagnostic tests for both bladder and colon cancers. These improved tests will allow a wider use of Matritech tests as screening tests for high risk groups. Effective cancer diagnostic tests will have significant benefit both in terms of saving human life and suffering, and in reducing the cost of healthcare. PROPOSED COMMERCIAL APPLICATION: The research described here will lead to almost immediate commercial application in the form of improved cancer diagnostic tests. By improving the overall accuracy of a cancer assay, in particular, by reducing the number of false positives, the market size for a particular test will increase. An accurate test that becomes used in a screening format has a significantly larger market than one that is used for monitoring.